Overcoming bacterial physical defenses with molecule-like ultrasmall antimicrobial gold nanoclusters

The size of metal nanoparticles (NPs) is crucial in their biomedical applications. Although abundant studies on the size effects of metal NPs in the range of 2-100 nm have been conducted, the exploration of the ultrasmall metal nanoclusters (NCs) of ~1 nm in size with unique features is quite limited. We synthesize three different sized gold (Au) NCs of different Au atom numbers and two bigger sized Au NPs protected by the same ligand to study the size influence on antimicrobial efficacy. The ultrasmall Au NCs can easily traverse the cell wall pores to be internalized inside bacteria, inducing reactive oxygen species generation to oxidize bacterial membrane and disturb bacterial metabolism. This explains why the Au NCs are antimicrobial while the Au NPs are non-antimicrobial, suggesting the key role of size in antimicrobial ability. Moreover, in contrast to the widely known size-dependent antimicrobial properties, the Au NCs of different atom numbers demonstrate molecule-like instead of size-dependent antimicrobial behavior with comparable effectiveness, indicating the unique molecule-like feature of ultrasmall Au NCs. Overcoming the bacterial defenses at the wall with ultrasmall Au NCs changes what was previously believed to harmless to the bacteria instead to a highly potent agent against the bacteria.